SPARC Up-Regulates Production and Pericellular Organization of Collagen I and Hyaluronan via TGF-β Signaling in Skin Fibroblasts
Masaki KOBAYASHI，Hiroyuki YOSHIDA*，Tomomi NAKAMURA，Kohei YAMAZAKI，Yoko ENDO，Tetsuya SAYO，Yoshito TAKAHASHI
Abstract:
Background: Secreted protein acidic and rich in cysteine (SPARC) regulates extracellular matrix (ECM) production,
interaction of cells with ECM and growth factor-dependent cell signaling. Here we examined SPARC’s effects on production
and pericellular organization of type I collagen and hyaluronan (HA) in normal human dermal fibroblasts.
Methods: Production of procollagen I and HA, and gene expression were analyzed by ELISA and quantitative real-time
PCR, respectively. The pericellular deposition of mature collagen I and HA was examined by immunocytochemistry.
Results: SPARC enhanced production of procollagen I and HA in fibroblasts by up-regulating mRNA expression of
COL1A1 (collagen α-1(I)) and HAS (HA synthase) 2/3, respectively. SPARC also increased the deposition of mature collagen
fibrils on the cell surface of fibroblasts, accompanying the increased mRNA expression of procollagen C-proteinase (BMP1)
and N-proteinase (ADAMTS2). The pericellular deposition of newly produced HA was also enhanced on the cell surface of
SPARC-treated fibroblasts. Furthermore, SPARC up-regulated TGF-β1 production in fibroblasts, and SPARC-induced procollagen I and HA production was abolished by blockade of TGF-β/Smad2/3 signaling.
Conclusion: SPARC simultaneously up-regulates production of procollagen I and HA in fibroblasts by up-regulating
Smad2/3-dependent TGF-β signaling, and also promotes the pericellular organization of mature collagen I fibrils and HA.